# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 8259 | 0 | 1.0000 | Secondary Metabolite Transcriptomic Pipeline (SeMa-Trap), an expression-based exploration tool for increased secondary metabolite production in bacteria. For decades, natural products have been used as a primary resource in drug discovery pipelines to find new antibiotics, which are mainly produced as secondary metabolites by bacteria. The biosynthesis of these compounds is encoded in co-localized genes termed biosynthetic gene clusters (BGCs). However, BGCs are often not expressed under laboratory conditions. Several genetic manipulation strategies have been developed in order to activate or overexpress silent BGCs. Significant increases in production levels of secondary metabolites were indeed achieved by modifying the expression of genes encoding regulators and transporters, as well as genes involved in resistance or precursor biosynthesis. However, the abundance of genes encoding such functions within bacterial genomes requires prioritization of the most promising ones for genetic manipulation strategies. Here, we introduce the 'Secondary Metabolite Transcriptomic Pipeline' (SeMa-Trap), a user-friendly web-server, available at https://sema-trap.ziemertlab.com. SeMa-Trap facilitates RNA-Seq based transcriptome analyses, finds co-expression patterns between certain genes and BGCs of interest, and helps optimize the design of comparative transcriptomic analyses. Finally, SeMa-Trap provides interactive result pages for each BGC, allowing the easy exploration and comparison of expression patterns. In summary, SeMa-Trap allows a straightforward prioritization of genes that could be targeted via genetic engineering approaches to (over)express BGCs of interest. | 2022 | 35580059 |
| 8398 | 1 | 0.9993 | ARTS 2.0: feature updates and expansion of the Antibiotic Resistant Target Seeker for comparative genome mining. Multi-drug resistant pathogens have become a major threat to human health and new antibiotics are urgently needed. Most antibiotics are derived from secondary metabolites produced by bacteria. In order to avoid suicide, these bacteria usually encode resistance genes, in some cases within the biosynthetic gene cluster (BGC) of the respective antibiotic compound. Modern genome mining tools enable researchers to computationally detect and predict BGCs that encode the biosynthesis of secondary metabolites. The major challenge now is the prioritization of the most promising BGCs encoding antibiotics with novel modes of action. A recently developed target-directed genome mining approach allows researchers to predict the mode of action of the encoded compound of an uncharacterized BGC based on the presence of resistant target genes. In 2017, we introduced the 'Antibiotic Resistant Target Seeker' (ARTS). ARTS allows for specific and efficient genome mining for antibiotics with interesting and novel targets by rapidly linking housekeeping and known resistance genes to BGC proximity, duplication and horizontal gene transfer (HGT) events. Here, we present ARTS 2.0 available at http://arts.ziemertlab.com. ARTS 2.0 now includes options for automated target directed genome mining in all bacterial taxa as well as metagenomic data. Furthermore, it enables comparison of similar BGCs from different genomes and their putative resistance genes. | 2020 | 32427317 |
| 9203 | 2 | 0.9992 | Dissecting the Role of Promoters of Pathogen-sensitive Genes in Plant Defense. Plants inherently show resistance to pathogen attack but are susceptible to multiple bacteria, viruses, fungi, and phytoplasmas. Diseases as a result of such infection leads to the deterioration of crop yield. Several pathogen-sensitive gene activities, promoters of such genes, associated transcription factors, and promoter elements responsible for crosstalk between the defense signaling pathways are involved in plant resistance towards a pathogen. Still, only a handful of genes and their promoters related to plant resistance have been identified to date. Such pathogen-sensitive promoters are accountable for elevating the transcriptional activity of certain genes in response to infection. Also, a suitable promoter is a key to devising successful crop improvement strategies as it ensures the optimum expression of the required transgene. The study of the promoters also helps in mining more details about the transcription factors controlling their activities and helps to unveil the involvement of new genes in the pathogen response. Therefore, the only way out to formulate new solutions is by analyzing the molecular aspects of these promoters in detail. In this review, we provided an overview of the promoter motifs and cis-regulatory elements having specific roles in pathogen attack response. To elaborate on the importance and get a vivid picture of the pathogen-sensitive promoter sequences, the key motifs and promoter elements were analyzed with the help of PlantCare and interpreted with available literature. This review intends to provide useful information for reconstructing the gene networks underlying the resistance of plants against pathogens. | 2020 | 33214765 |
| 9617 | 3 | 0.9992 | Multiplex CRISPRi System Enables the Study of Stage-Specific Biofilm Genetic Requirements in Enterococcus faecalis. Enterococcus faecalis is an opportunistic pathogen, which can cause multidrug-resistant life-threatening infections. Gaining a complete understanding of enterococcal pathogenesis is a crucial step in identifying a strategy to effectively treat enterococcal infections. However, bacterial pathogenesis is a complex process often involving a combination of genes and multilevel regulation. Compared to established knockout methodologies, CRISPR interference (CRISPRi) approaches enable the rapid and efficient silencing of genes to interrogate gene products and pathways involved in pathogenesis. As opposed to traditional gene inactivation approaches, CRISPRi can also be quickly repurposed for multiplexing or used to study essential genes. Here, we have developed a novel dual-vector nisin-inducible CRISPRi system in E. faecalis that can efficiently silence via both nontemplate and template strand targeting. Since the nisin-controlled gene expression system is functional in various Gram-positive bacteria, the developed CRISPRi tool can be extended to other genera. This system can be applied to study essential genes, genes involved in antimicrobial resistance, and genes involved in biofilm formation and persistence. The system is robust and can be scaled up for high-throughput screens or combinatorial targeting. This tool substantially enhances our ability to study enterococcal biology and pathogenesis, host-bacterium interactions, and interspecies communication.IMPORTANCEEnterococcus faecalis causes multidrug-resistant life-threatening infections and is often coisolated with other pathogenic bacteria from polymicrobial biofilm-associated infections. Genetic tools to dissect complex interactions in mixed microbial communities are largely limited to transposon mutagenesis and traditional time- and labor-intensive allelic-exchange methods. Built upon streptococcal dCas9, we developed an easily modifiable, inducible CRISPRi system for E. faecalis that can efficiently silence single and multiple genes. This system can silence genes involved in biofilm formation and antibiotic resistance and can be used to interrogate gene essentiality. Uniquely, this tool is optimized to study genes important for biofilm initiation, maturation, and maintenance and can be used to perturb preformed biofilms. This system will be valuable to rapidly and efficiently investigate a wide range of aspects of complex enterococcal biology. | 2020 | 33082254 |
| 8286 | 4 | 0.9992 | RNA Modifications in Pathogenic Bacteria: Impact on Host Adaptation and Virulence. RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to adaptive processes. RNA modifications play multiple functions since they can impact RNA base-pairings, recognition by proteins, decoding, as well as RNA structure and stability. However, their roles in stress, environmental adaptation and during infections caused by pathogenic bacteria have just started to be appreciated. With the development of modern technologies in mass spectrometry and deep sequencing, recent examples of modifications regulating host-pathogen interactions have been demonstrated. They show how RNA modifications can regulate immune responses, antibiotic resistance, expression of virulence genes, and bacterial persistence. Here, we illustrate some of these findings, and highlight the strategies used to characterize RNA modifications, and their potential for new therapeutic applications. | 2021 | 34440299 |
| 8243 | 5 | 0.9992 | Rooteomics: the challenge of discovering plant defense-related proteins in roots. In recent years, a strong emphasis has been given in deciphering the function of genes unraveled by the completion of several genome sequencing projects. In plants, functional genomics has been massively used in order to search for gene products of agronomic relevance. As far as root-pathogen interactions are concerned, several genes are recognized to provide tolerance/resistance against potential invaders. However, very few proteins have been identified by using current proteomic approaches. One of the major drawbacks for the successful analysis of root proteomes is the inherent characteristics of this tissue, which include low volume content and high concentration of interfering substances such as pigments and phenolic compounds. The proteome analysis of plant-pathogen interactions provides important information about the global proteins expressed in roots in response to biotic stresses. Moreover, several pathogenic proteins superimpose the plant proteome and can be identified and used as targets for the control of viruses, bacteria, fungi and nematode pathogens. The present review focuses on advances in different proteomic strategies dedicated to the challenging analysis of plant defense proteins expressed during bacteria-, fungi- and nematode-root interactions. Recent developments, limitations of the current techniques, and technological perspectives for root proteomics aiming at the identification of resistance-related proteins are discussed. | 2008 | 18393883 |
| 9214 | 6 | 0.9992 | Enabling genetic analysis of diverse bacteria with Mobile-CRISPRi. The vast majority of bacteria, including human pathogens and microbiome species, lack genetic tools needed to systematically associate genes with phenotypes. This is the major impediment to understanding the fundamental contributions of genes and gene networks to bacterial physiology and human health. Clustered regularly interspaced short palindromic repeats interference (CRISPRi), a versatile method of blocking gene expression using a catalytically inactive Cas9 protein (dCas9) and programmable single guide RNAs, has emerged as a powerful genetic tool to dissect the functions of essential and non-essential genes in species ranging from bacteria to humans(1-6). However, the difficulty of establishing effective CRISPRi systems across bacteria is a major barrier to its widespread use to dissect bacterial gene function. Here, we establish 'Mobile-CRISPRi', a suite of CRISPRi systems that combines modularity, stable genomic integration and ease of transfer to diverse bacteria by conjugation. Focusing predominantly on human pathogens associated with antibiotic resistance, we demonstrate the efficacy of Mobile-CRISPRi in gammaproteobacteria and Bacillales Firmicutes at the individual gene scale, by examining drug-gene synergies, and at the library scale, by systematically phenotyping conditionally essential genes involved in amino acid biosynthesis. Mobile-CRISPRi enables genetic dissection of non-model bacteria, facilitating analyses of microbiome function, antibiotic resistances and sensitivities, and comprehensive screens for host-microorganism interactions. | 2019 | 30617347 |
| 9200 | 7 | 0.9992 | Application of the CRISPR/Cas System for Generation of Pathogen-Resistant Plants. The use of the CRISPR/Cas9 prokaryotic adaptive immune system has led to a breakthrough in targeted genome editing in eukaryotes. The CRISPR/Cas technology allows to generate organisms with desirable characteristics by introducing deletions/insertions into selected genome loci resulting in the knockout or modification of target genes. This review focuses on the current state of the CRISPR/Cas use for the generation of plants resistant to viruses, bacteria, and parasitic fungi. Resistance to DNA- and RNA-containing viruses is usually provided by expression in transgenic plants of the Cas endonuclease gene and short guide RNAs (sgRNAs) targeting certain sites in the viral or the host plant genomes to ensure either direct cleavage of the viral genome or modification of the plant host genome in order to decrease the efficiency of virus replication. Editing of plant genes involved in the defense response to pathogens increases plants resistance to bacteria and pathogenic fungi. The review explores strategies and prospects of the development of pathogen-resistant plants with a focus on the generation of non-transgenic (non-genetically modified) organisms, in particular, by using plasmid (DNA)-free systems for delivery of the Cas/sgRNA editing complex into plant cells. | 2018 | 30878030 |
| 308 | 8 | 0.9992 | Linearmycins Activate a Two-Component Signaling System Involved in Bacterial Competition and Biofilm Morphology. Bacteria use two-component signaling systems to adapt and respond to their competitors and changing environments. For instance, competitor bacteria may produce antibiotics and other bioactive metabolites and sequester nutrients. To survive, some species of bacteria escape competition through antibiotic production, biofilm formation, or motility. Specialized metabolite production and biofilm formation are relatively well understood for bacterial species in isolation. How bacteria control these functions when competitors are present is not well studied. To address fundamental questions relating to the competitive mechanisms of different species, we have developed a model system using two species of soil bacteria, Bacillus subtilis and Streptomyces sp. strain Mg1. Using this model, we previously found that linearmycins produced by Streptomyces sp. strain Mg1 cause lysis of B. subtilis cells and degradation of colony matrix. We identified strains of B. subtilis with mutations in the two-component signaling system yfiJK operon that confer dual phenotypes of specific linearmycin resistance and biofilm morphology. We determined that expression of the ATP-binding cassette (ABC) transporter yfiLMN operon, particularly yfiM and yfiN, is necessary for biofilm morphology. Using transposon mutagenesis, we identified genes that are required for YfiLMN-mediated biofilm morphology, including several chaperones. Using transcriptional fusions, we found that YfiJ signaling is activated by linearmycins and other polyene metabolites. Finally, using a truncated YfiJ, we show that YfiJ requires its transmembrane domain to activate downstream signaling. Taken together, these results suggest coordinated dual antibiotic resistance and biofilm morphology by a single multifunctional ABC transporter promotes competitive fitness of B. subtilisIMPORTANCE DNA sequencing approaches have revealed hitherto unexplored diversity of bacterial species in a wide variety of environments that includes the gastrointestinal tract of animals and the rhizosphere of plants. Interactions between different species in bacterial communities have impacts on our health and industry. However, many approaches currently used to study whole bacterial communities do not resolve mechanistic details of interspecies interactions, including how bacteria sense and respond to their competitors. Using a competition model, we have uncovered dual functions for a previously uncharacterized two-component signaling system involved in specific antibiotic resistance and biofilm morphology. Insights gleaned from signaling within interspecies interaction models build a more complete understanding of gene functions important for bacterial communities and will enhance community-level analytical approaches. | 2017 | 28461449 |
| 9235 | 9 | 0.9992 | Investigating the Genomic Background of CRISPR-Cas Genomes for CRISPR-Based Antimicrobials. CRISPR-Cas systems are an adaptive immunity that protects prokaryotes against foreign genetic elements. Genetic templates acquired during past infection events enable DNA-interacting enzymes to recognize foreign DNA for destruction. Due to the programmability and specificity of these genetic templates, CRISPR-Cas systems are potential alternative antibiotics that can be engineered to self-target antimicrobial resistance genes on the chromosome or plasmid. However, several fundamental questions remain to repurpose these tools against drug-resistant bacteria. For endogenous CRISPR-Cas self-targeting, antimicrobial resistance genes and functional CRISPR-Cas systems have to co-occur in the target cell. Furthermore, these tools have to outplay DNA repair pathways that respond to the nuclease activities of Cas proteins, even for exogenous CRISPR-Cas delivery. Here, we conduct a comprehensive survey of CRISPR-Cas genomes. First, we address the co-occurrence of CRISPR-Cas systems and antimicrobial resistance genes in the CRISPR-Cas genomes. We show that the average number of these genes varies greatly by the CRISPR-Cas type, and some CRISPR-Cas types (IE and IIIA) have over 20 genes per genome. Next, we investigate the DNA repair pathways of these CRISPR-Cas genomes, revealing that the diversity and frequency of these pathways differ by the CRISPR-Cas type. The interplay between CRISPR-Cas systems and DNA repair pathways is essential for the acquisition of new spacers in CRISPR arrays. We conduct simulation studies to demonstrate that the efficiency of these DNA repair pathways may be inferred from the time-series patterns in the RNA structure of CRISPR repeats. This bioinformatic survey of CRISPR-Cas genomes elucidates the necessity to consider multifaceted interactions between different genes and systems, to design effective CRISPR-based antimicrobials that can specifically target drug-resistant bacteria in natural microbial communities. | 2022 | 35692726 |
| 8245 | 10 | 0.9992 | Plant Elite Squad: First Defense Line and Resistance Genes - Identification, Diversity and Functional Roles. Plants exhibit sensitive mechanisms to respond to environmental stresses, presenting some specific and non-specific reactions when attacked by pathogens, including organisms from different classes and complexity, as viroids, viruses, bacteria, fungi and nematodes. A crucial step to define the fate of the plant facing an invading pathogen is the activation of a compatible Resistance (R) gene, the focus of the present review. Different aspects regarding R-genes and their products are discussed, including pathogen recognition mechanisms, signaling and effects on induced and constitutive defense processes, splicing and post transcriptional mechanisms involved. There are still countless challenges to the complete understanding of the mechanisms involving R-genes in plants, in particular those related to the interactions with other genes of the pathogen and of the host itself, their regulation, acting mechanisms at transcriptional and post-transcriptional levels, as well as the influence of other types of stress over their regulation. A magnification of knowledge is expected when considering the novel information from the omics and systems biology. | 2017 | 27455974 |
| 9607 | 11 | 0.9992 | Transcriptome-Level Signatures in Gene Expression and Gene Expression Variability during Bacterial Adaptive Evolution. Antibiotic-resistant bacteria are an increasingly serious public health concern, as strains emerge that demonstrate resistance to almost all available treatments. One factor that contributes to the crisis is the adaptive ability of bacteria, which exhibit remarkable phenotypic and gene expression heterogeneity in order to gain a survival advantage in damaging environments. This high degree of variability in gene expression across biological populations makes it a challenging task to identify key regulators of bacterial adaptation. Here, we research the regulation of adaptive resistance by investigating transcriptome profiles of Escherichia coli upon adaptation to disparate toxins, including antibiotics and biofuels. We locate potential target genes via conventional gene expression analysis as well as using a new analysis technique examining differential gene expression variability. By investigating trends across the diverse adaptation conditions, we identify a focused set of genes with conserved behavior, including those involved in cell motility, metabolism, membrane structure, and transport, and several genes of unknown function. To validate the biological relevance of the observed changes, we synthetically perturb gene expression using clustered regularly interspaced short palindromic repeat (CRISPR)-dCas9. Manipulation of select genes in combination with antibiotic treatment promotes adaptive resistance as demonstrated by an increased degree of antibiotic tolerance and heterogeneity in MICs. We study the mechanisms by which identified genes influence adaptation and find that select differentially variable genes have the potential to impact metabolic rates, mutation rates, and motility. Overall, this work provides evidence for a complex nongenetic response, encompassing shifts in gene expression and gene expression variability, which underlies adaptive resistance. IMPORTANCE Even initially sensitive bacteria can rapidly thwart antibiotic treatment through stress response processes known as adaptive resistance. Adaptive resistance fosters transient tolerance increases and the emergence of mutations conferring heritable drug resistance. In order to extend the applicable lifetime of new antibiotics, we must seek to hinder the occurrence of bacterial adaptive resistance; however, the regulation of adaptation is difficult to identify due to immense heterogeneity emerging during evolution. This study specifically seeks to generate heterogeneity by adapting bacteria to different stresses and then examines gene expression trends across the disparate populations in order to pinpoint key genes and pathways associated with adaptive resistance. The targets identified here may eventually inform strategies for impeding adaptive resistance and prolonging the effectiveness of antibiotic treatment. | 2017 | 28217741 |
| 8281 | 12 | 0.9991 | Exploring multiple drug and herbicide resistance in plants--spotlight on transporter proteins. Multiple drug resistance (MDR) has been extensively studied in bacteria, yeast, and mammalian cells due to the great clinical significance of this problem. MDR is not well studied in plant systems, although plant genomes contain large numbers of genes encoding putative MDR transporters (MDRTs). Biochemical pathways in the chloroplast are the targets of many herbicides and antibiotics, yet very little data is available regarding mechanisms of drug transport across the chloroplast membrane. MDRTs typically have broad substrate specificities, and may transport essential compounds and metabolites in addition to toxins. Indeed, plant transporters belonging to MDR families have also been implicated in the transport of a wide variety of compounds including auxins, flavonoids, glutathione conjugates, metal chelators, herbicides and antibiotics, although definitive evidence that a single transporter is capable of moving both toxins and metabolites has not yet been provided. Current understanding of plant MDR can be expanded via the characterization of candidate genes, especially MDRTs predicted to localize to the chloroplast, and also via traditional forward genetic approaches. Novel plant MDRTs have the potential to become endogenous selectable markers, aid in phytoremediation strategies, and help us to understand how plants have evolved to cope with toxins in their environment. | 2011 | 21421361 |
| 9219 | 13 | 0.9991 | Knowing and Naming: Phage Annotation and Nomenclature for Phage Therapy. Bacteriophages, or phages, are viruses that infect bacteria shaping microbial communities and ecosystems. They have gained attention as potential agents against antibiotic resistance. In phage therapy, lytic phages are preferred for their bacteria killing ability, while temperate phages, which can transfer antibiotic resistance or toxin genes, are avoided. Selection relies on plaque morphology and genome sequencing. This review outlines annotating genomes, identifying critical genomic features, and assigning functional labels to protein-coding sequences. These annotations prevent the transfer of unwanted genes, such as antimicrobial resistance or toxin genes, during phage therapy. Additionally, it covers International Committee on Taxonomy of Viruses (ICTV)-an established phage nomenclature system for simplified classification and communication. Accurate phage genome annotation and nomenclature provide insights into phage-host interactions, replication strategies, and evolution, accelerating our understanding of the diversity and evolution of phages and facilitating the development of phage-based therapies. | 2023 | 37932119 |
| 8402 | 14 | 0.9991 | Exploring phage-host interactions in Burkholderia cepacia complex bacterium to reveal host factors and phage resistance genes using CRISPRi functional genomics and transcriptomics. Complex interactions of bacteriophages with their bacterial hosts determine phage host range and infectivity. While phage defense systems and host factors have been identified in model bacteria, they remain challenging to predict in non-model bacteria. In this paper, we integrate functional genomics and transcriptomics to investigate phage-host interactions, revealing active phage resistance and host factor genes in Burkholderia cenocepacia K56-2. Burkholderia cepacia complex species are commonly found in soil and are opportunistic pathogens in immunocompromised patients. We studied infection of B. cenocepacia K56-2 with Bcep176, a temperate phage isolated from Burkholderia multivorans. A genome-wide dCas9 knockdown library targeting B. cenocepacia K56-2 was constructed, and a pooled infection experiment identified 63 novel genes or operons coding for candidate host factors or phage resistance genes. The activities of a subset of candidate host factor and resistance genes were validated via single-gene knockdowns. Transcriptomics of B. cenocepacia K56-2 during Bcep176 infection revealed that expression of genes coding for host factor and resistance candidates identified in this screen was significantly altered during infection by 4 h post-infection. Identifying which bacterial genes are involved in phage infection is important to understand the ecological niches of B. cenocepacia and its phages, and for designing phage therapies.IMPORTANCEBurkholderia cepacia complex bacteria are opportunistic pathogens inherently resistant to antibiotics, and phage therapy is a promising alternative treatment for chronically infected patients. Burkholderia bacteria are also ubiquitous in soil microbiomes. To develop improved phage therapies for pathogenic Burkholderia bacteria, or engineer phages for applications, such as microbiome editing, it's essential to know the bacterial host factors required by the phage to kill bacteria, as well as how the bacteria prevent phage infection. This work identified 65 genes involved in phage-host interactions in Burkholderia cenocepacia K56-2 and tracked their expression during infection. These findings establish a knowledge base to select and engineer phages infecting or transducing Burkholderia bacteria. | 2025 | 41036840 |
| 8267 | 15 | 0.9991 | Why put up with immunity when there is resistance: an excursion into the population and evolutionary dynamics of restriction-modification and CRISPR-Cas. Bacteria can readily generate mutations that prevent bacteriophage (phage) adsorption and thus make bacteria resistant to infections with these viruses. Nevertheless, the majority of bacteria carry complex innate and/or adaptive immune systems: restriction-modification (RM) and CRISPR-Cas, respectively. Both RM and CRISPR-Cas are commonly assumed to have evolved and be maintained to protect bacteria from succumbing to infections with lytic phage. Using mathematical models and computer simulations, we explore the conditions under which selection mediated by lytic phage will favour such complex innate and adaptive immune systems, as opposed to simple envelope resistance. The results of our analysis suggest that when populations of bacteria are confronted with lytic phage: (i) In the absence of immunity, resistance to even multiple bacteriophage species with independent receptors can evolve readily. (ii) RM immunity can benefit bacteria by preventing phage from invading established bacterial populations and particularly so when there are multiple bacteriophage species adsorbing to different receptors. (iii) Whether CRISPR-Cas immunity will prevail over envelope resistance depends critically on the number of steps in the coevolutionary arms race between the bacteria-acquiring spacers and the phage-generating CRISPR-escape mutants. We discuss the implications of these results in the context of the evolution and maintenance of RM and CRISPR-Cas and highlight fundamental questions that remain unanswered. This article is part of a discussion meeting issue 'The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems'. | 2019 | 30905282 |
| 8285 | 16 | 0.9991 | Bacterial stress response: understanding the molecular mechanics to identify possible therapeutic targets. INTRODUCTION: Bacteria are ubiquitous and many of them are pathogenic in nature. Entry of bacteria in host and its recognition by host defense system induce stress in host cells. With time, bacteria have also developed strategies including drug resistance to escape from antibacterial therapy as well as host defense mechanism. AREAS COVERED: Bacterial stress initiates and promotes adaptive immune response through several integrated mechanisms. The mechanisms of bacteria to up and down regulate different pathways involved in these responses have been discussed. The genetic expression of these pathways can be manipulated by the pharmacological interventions. Present review discusses in these contexts and explores the possibilities to overcome stress induced by bacterial pathogens and to suggest new possible therapeutic targets. EXPERT OPINION: In our opinion, there are two important fronts to regulate the bacterial stress. One is to target caspase involved in the process of transformation and translation at gene level and protein expression. Second is the identification of bacterial genes that lead to synthesis of abnormal end products supporting bacterial survival in host environment and also to surpass the host defense mechanism. Identification of such genes and their expression products could be an effective option to encounter bacterial resistance. | 2021 | 32811215 |
| 9204 | 17 | 0.9991 | Susceptibility Genes in Bacterial Diseases of Plants. Plant susceptibility (S) genes exploited by pathogenic bacteria play critical roles in disease development, collectively contributing to symptoms, pathogen proliferation, and spread. S genes may support pathogen establishment within the host, suppress host immunity, regulate host physiology or development, or function in other ways. S genes can be passive, e.g., involved in pathogen attraction or required for pathogen effector localization or activity, or active, contributing directly to symptoms or pathogen proliferation. Knowledge of S genes is important for understanding disease and other aspects of plant biology. It is also useful for disease management, as nonfunctional alleles can slow or prevent disease and, because they are often quantitative, can exert less selection on pathogens than dominant resistance genes, allowing greater durability. In this review, we discuss bacterial exploitation of S genes, S-gene functional diversity, approaches for identifying S genes, translation of S-gene knowledge for disease control, and future perspectives on this exciting area of plant pathology. | 2025 | 40446167 |
| 8271 | 18 | 0.9991 | Genome-Wide Sensitivity Analysis of the Microsymbiont Sinorhizobium meliloti to Symbiotically Important, Defensin-Like Host Peptides. The model legume species Medicago truncatula expresses more than 700 nodule-specific cysteine-rich (NCR) signaling peptides that mediate the differentiation of Sinorhizobium meliloti bacteria into nitrogen-fixing bacteroids. NCR peptides are essential for a successful symbiosis in legume plants of the inverted-repeat-lacking clade (IRLC) and show similarity to mammalian defensins. In addition to signaling functions, many NCR peptides exhibit antimicrobial activity in vitro and in vivo Bacterial resistance to these antimicrobial activities is likely to be important for symbiosis. However, the mechanisms used by S. meliloti to resist antimicrobial activity of plant peptides are poorly understood. To address this, we applied a global genetic approach using transposon mutagenesis followed by high-throughput sequencing (Tn-seq) to identify S. meliloti genes and pathways that increase or decrease bacterial competitiveness during exposure to the well-studied cationic NCR247 peptide and also to the unrelated model antimicrobial peptide polymyxin B. We identified 78 genes and several diverse pathways whose interruption alters S. meliloti resistance to NCR247. These genes encode the following: (i) cell envelope polysaccharide biosynthesis and modification proteins, (ii) inner and outer membrane proteins, (iii) peptidoglycan (PG) effector proteins, and (iv) non-membrane-associated factors such as transcriptional regulators and ribosome-associated factors. We describe a previously uncharacterized yet highly conserved peptidase, which protects S. meliloti from NCR247 and increases competitiveness during symbiosis. Additionally, we highlight a considerable number of uncharacterized genes that provide the basis for future studies to investigate the molecular basis of symbiotic development as well as chronic pathogenic interactions.IMPORTANCE Soil rhizobial bacteria enter into an ecologically and economically important symbiotic interaction with legumes, in which they differentiate into physiologically distinct bacteroids that provide essential ammonia to the plant in return for carbon sources. Plant signal peptides are essential and specific to achieve these physiological changes. These peptides show similarity to mammalian defensin peptides which are part of the first line of defense to control invading bacterial populations. A number of these legume peptides are indeed known to possess antimicrobial activity, and so far, only the bacterial BacA protein is known to protect rhizobial bacteria against their antimicrobial action. This study identified numerous additional bacterial factors that mediate protection and belong to diverse biological pathways. Our results significantly contribute to our understanding of the molecular roles of bacterial factors during legume symbioses and, second, provide insights into the mechanisms that pathogenic bacteria may use to resist the antimicrobial effects of defensins during infections. | 2017 | 28765224 |
| 9623 | 19 | 0.9991 | Prokaryotic toxin-antitoxin systems--the role in bacterial physiology and application in molecular biology. Bacteria have developed multiple complex mechanisms ensuring an adequate response to environmental changes. In this context, bacterial cell division and growth are subject to strict control to ensure metabolic balance and cell survival. A plethora of studies cast light on toxin-antitoxin (TA) systems as metabolism regulators acting in response to environmental stress conditions. Many of those studies suggest direct relations between the TA systems and the pathogenic potential or antibiotic resistance of relevant bacteria. Other studies point out that TA systems play a significant role in ensuring stability of mobile genetic material. The evolutionary origin and relations between various TA systems are still a subject of a debate. The impact of toxin-antitoxin systems on bacteria physiology prompted their application in molecular biology as tools allowing cloning of some hard-to-maintain genes, plasmid maintenance and production of recombinant proteins. | 2011 | 21394325 |